Electronic Measurements of Single-Molecule Processing by DNA Polymerase I (Klenow Fragment).

Bioconjugating single molecules of the Klenow fragment of DNA polymerase I into electronic nanocircuits allowed electrical recordings of enzymatic function and dynamic variability with the resolution of individual nucleotide incorporation events. Continuous recordings of DNA polymerase processing mu...

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Publicado en:Journal of the American Chemical Society Vol. 135; no. 21; pp. 7855 - 7861
Autores principales: Olsen, Tivoli J., Yongki Choi, Sims, Patrick C., Tolga Gul, O., Corso, Brad L., Chengjun Dong, Brown, William A., Collins, Philip G., Weiss, Gregory A.
Formato: Artículo
Publicado: American Chemical Society 5/29/2013
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Acceso en línea:Ver este registro en EBSCOhost
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      dt: 5/29/2013
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        10.1021/ja311603r
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        atl: Electronic Measurements of Single-Molecule Processing by DNA Polymerase I (Klenow Fragment).
      aug:
        au:
          Olsen, Tivoli J.
          Yongki Choi
          Sims, Patrick C.
          Tolga Gul, O.
          Corso, Brad L.
          Chengjun Dong
          Brown, William A.
          Collins, Philip G.
          Weiss, Gregory A.
        affil:
          Department of Chemistry, University of California, Irvine, California 92697, United States
          Department of Physics and Astronomy, University of California, Irvine, California 92697, United States
          Department of Molecular Biology, University of California, Irvine, California 92697, United States
      su:
        DNA polymerases kinetics
        Single molecule research
        Biochemical templates
        Bioconjugates
        Electronic measurements
        Nucleotides
        Phosphodiesters
      sug:
        subj:
          DNA polymerases kinetics
          Single molecule research
          Biochemical templates
          Bioconjugates
          Electronic measurements
          Nucleotides
          Phosphodiesters
      ab: Bioconjugating single molecules of the Klenow fragment of DNA polymerase I into electronic nanocircuits allowed electrical recordings of enzymatic function and dynamic variability with the resolution of individual nucleotide incorporation events. Continuous recordings of DNA polymerase processing multiple homopolymeric DNA templates extended over 600 s and through >10 000 bond-forming events. An enzymatic processivity of 42 nucleotides for a template of the same length was directly observed. Statistical analysis determined key kinetic parameters for the enzyme's open and closed conformations. Consistent with these nanocircuit-based observations, the enzyme's closed complex forms a phosphodiester bond in a highly efficient process >99.8% of the time, with a mean duration of only 0.3 ms for all four dNTPs. The rate-limiting step for catalysis occurs during the enzyme's open state, but with a nearly 2-fold longer duration for dATP or dTTP incorporation than for dCTP or dGTP into complementary, homopolymeric DNA templates. Taken together, the results provide a wealth of new information complementing prior work on the mechanism and dynamics of DNA polymerase I.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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          year: 2013
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